Two populations of neuronal intranuclear inclusions in SCA7 differ in size and promyelocytic leukaemia protein content.

J. Takahashi
Brain. 2002-07-01; 125(7): 1534-1543
DOI: 10.1093/brain/awf154

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1. Brain. 2002 Jul;125(Pt 7):1534-43.

Two populations of neuronal intranuclear inclusions in SCA7 differ in size and
promyelocytic leukaemia protein content.

Takahashi J(1), Fujigasaki H, Zander C, El Hachimi KH, Stevanin G, Dürr A, Lebre
AS, Yvert G, Trottier Y, de Thé H, Hauw JJ, Duyckaerts C, Brice A.

Author information:
(1)Laboratoire de Neuropathologie Raymond Escourolle, Paris, France.

Spinocerebellar ataxia type 7 (SCA7) is a hereditary progressive cerebellar
ataxia with retinal degeneration associated with an abnormally expanded
polyglutamine stretch. Neuronal intranuclear inclusions (NIIs), as in other
polyglutamine diseases, are pathological hallmarks of these disorders. NIIs in
polyglutamine diseases contain not only the protein with the expanded
polyglutamine stretch but also other types of proteins. Several chaperone
proteins related to the ubiquitin proteasome pathway, transcription factors and
nuclear matrix proteins have been detected in NIIs. The composition of NIIs might
reflect the process of NII formation and part of the pathogenesis of these
diseases. To investigate how these proteins relate to the pathogenesis of SCA7,
we performed immunohistochemical analyses of the composition of NIIs in two cases
of SCA7. We demonstrated that there are two types of NIIs in SCA7 that differ in
size and immunoreactivity to promyelocytic leukaemia protein (PML), one of the
essential components of nuclear bodies (NBs; also called PML oncogenic domains).
Small and large NIIs contained ataxin-7, human DnaJ homologue 2 (HDJ-2) and
proteasome subunit 19S. In contrast, PML was found only in small NIIs.
CREB-binding protein (CBP), another component of NBs, was distributed like PML in
NIIs. Our results suggest that NIIs are formed by the accumulation of ataxin-7 in
NBs, which become enlarged as they recruit related proteins.

DOI: 10.1093/brain/awf154
PMID: 12077003 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus